Deep Mining of Oxysterols and Cholestenoic Acids in Human Plasma and Cerebrospinal Fluid: Quantification using Isotope Dilution Mass Spectrometry

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography – tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient

Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3

GATA-3 is essential for T cell development from the earliest stages. However, abundant GATA-3 can drive T lineage precursors to a non–T cell fate, depending on Notch signaling and developmental stage. Here, overexpression of GATA-3 blocked the survival of pro–T cells when Notch-Delta signals were present but enhanced viability in their absence. In fetal thymocytes at the double-negative 1 (DN1) stage and DN2 stage but not those at the DN3 stage, overexpression of GATA-3 rapidly induced respecification to the mast cell lineage with high frequency by direct transcriptional 'reprogramming'. Normal DN2 thymocytes also showed mast cell potential when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro–T cell and mast cell programs and a previously unknown function for Notch in T lineage fidelity

Effect of ventilation in enclosure machine system on MWF aerosol properties

In this paper the influence of ventilation air velocity on properties of metal working fluids (MWF) aerosol/mist is presented. Aerosol characteristics were monitored in the chamber as well as at the entrance of ventilation pipe by optical particle size analyzer. Aerosol was generated from 6% water emulsion of three commercial MWF. Four different velocities, less than the velocity of secondary atomization, were examined (1, 3, 6, 8 m/s). Droplets size distribution, mass concentration (mg/m3), as well as number concentration (P/cm3) were measured and analyzed. From the results obtained it may be seen that coalescence is more pronounced as the velocity increases, although the number concentration decreases, due to higher air dilution. Therefore, more droplets are in a whirling motion at higher air velocities, hence more random collisions are possible. Further analysis shows that there is one value of air velocity under which the maximum difference between the aerosol in chamber and the aerosol at the entrance of the pipe can be observed. This velocity could be named specific velocity and depends on the given aerosol properties. It could be assumed that specific velocity is conditioned by the properties of oil from which emulsion is prepared. Oil viscosity and molar mass have greatest influence on the specific velocity

Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid:quantification using isotope dilution mass spectrometry

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography - tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient.</p

Business Modeling and Flexibility in Software-Intensive Product Development - A Systematic Literature Review

International audienceContinuously achieving and maintaining competitive advantage is the critical survival factor for software-intensive product development companies undergoing digitalization transformation. These companies remain uncertain if investments in business modeling is sufficient to cope with rapidly changing business models, technology, and customer demands. We conducted a Systematic Literature Review using the snowballing methodology to explore the effects of business modeling on business flexibility and variability in the realization. Our results confirm a research gap regarding translating desired strategic flexibility into business options that can efficiently and effectively be implemented using software-based variability in the realization. We conclude that more research is needed consolidating business model innovation, experimentation, and operationalization. Building on theories for learning and knowledge creation, we propose a framework for describing change and analyzing strategic, tactical and operational choices in business model experimentation

Brachiopod palaeobiogeography in the western Tethys during the Early Jurassic diversity maximum: introduction of a Pontic Province

The biogeography of Pliensbachian (Early Jurassic) brachiopods in western Tethys is investigated using complementary multivariate tools including metric and non-metric ordination, additive cluster and bootstrapped spanning network analyses, as well as one-way analysis of similarity and similarity percentage analysis. All analyses were conducted using the Dice and Simpson similarity indices for presence/absence data on occurrence datasets involving 24 assemblages homogenized at the species level, including (403 taxa) or excluding (210 taxa) species found in only one assemblage. The analyses present a highly consistent biogeographical picture involving three main clusters: the Euro-Boreal, Mediterranean and Pontic biochores. The brachiopod species typical of the newly defined Pontic biochore are illustrated. The three assemblages from the Atlas area are interpreted as a fourth biochore, compositionally intermediate between those of the Euro-Boreal and Mediterranean. The Mediterranean biochore can be further divided into an intra- and a peri-Mediterranean group. These five, palaeogeographically well-constrained biochores show moderate to high degrees of species endemicity, ranging from 20% (Atlas) to 58% (Euro-Boreal). Based on available evidence, and after a reasonable cutback of the customary scale of ranks, the following biogeographical categories and names are suggested for the western Tethyan Pliensbachian brachiopod biochores: Euro-Boreal Province, Mediterranean Province (including an intra-Mediterranean and a peri-Mediterranean Subprovince), Pontic Province and Atlas Subprovince. In addition, a still poorly documented brachiopod biochore occurs on the Gondwana margin as a possible precursor of the extensive Middle to Late Jurassic Ethiopian Province